Mechanism of Toxic Cell Death Flashcards

1
Q

What are the mechanisms of toxic cell death?

A

Impaired ATP synthesis; alteration of Ca gradients; other mechanisms–damage to cell membrane, cytoskeleton, or protein synthesis

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2
Q

How can ATP synthesis be impaired?

A

interfering with delivery of electrons; delivery of oxygen; ETC function; ATP synthase inhibition; uncouplers

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3
Q

what impairs delivery of electrons?

A

i. Fluoracetate–inhibits aconitase in the CAC
ii. Used as to kill rodents
Can’t deliver e-s to ETC–>no ATP production

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4
Q

what impairs delivery of oxygen?

A

i. Carbon monoxide
ii. Outcompetes O2 for hemoglobin
iii. Blocks delivery of O2 to mitochondria for the ETC

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5
Q

what impairs ETC function?

A

i. E.g. cyanide
1) Inhibits cytochrome oxidase
ii. E.g. rotenone–inhibits NADH coenzyme Q reducase

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6
Q

what inihibts ATP synthase?

A

d. Chlordecone
i. Insectiside
Same class as DDT–can’t phos ADP to ATP

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7
Q

what are the uncouplers?

A

i. Disrupt proton gradient
ii. E.g. pesticide called pentachlorophenol (PCPs)
iii. Fungicide
iv. Dinitrophenols

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8
Q

what is pentachlorophenol?

A

???

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9
Q

what are fungicides and how do they disturb cell membranes?

A

iii. Fungicide
1) Treating for lumber
2) Washes off into streams, kills fish
3) “ionophore”–makes membrane leaky to protons

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10
Q

what are dinitrophenols?

A

1) Donate protons in inner mitochondrial space

Reduce the gradient

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11
Q

alteration of Ca gradients

A

iv. 10 000x more ECF Ca than ICF Ca
1) When you open up the Ca “dam”, Ca floods in
v. Main mechanism: xenos alter plasma membrane permeability to Ca
1) Damage to membrane, to active transport that pumps Ca out
Major target: mitochondrial Ca (not SR Ca

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12
Q

how do nonpolar solvents cause toxic cell death?

A

1) Lipid sol solvents
2) Alter the fluidity of membrane
a) E.g. like cholesterol

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13
Q

how can the cytoskeleton be destroyed?

A

1) Scaffolding

2) Cholchecine–destroys spindle fibres (important in cell divison–inhibits mitosis)

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14
Q

how can protein synthesis be interfered with?

A

1) Ethanol
a) This is why you don’t take tylenol with a hangover
b) If you have been binge drinking, protein synthesis has been shut down–>especially glutathione

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